文獻一（英文）：Corpechot C, Barbu V, Chazouillères O，et al. Genetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders. Liver Int, 2020;40(1):163-174. Impact factor= 5.542, Q2區。
文獻一（中文）：Corpechot C, Barbu V, Chazouillères O等。ABCC2對Dubin-Johnson症候群和遺傳性膽汁淤積性疾病的遺傳貢獻.國際肝病, 2020; 40(1):163-174. 影響因子= 5.542, Q2區。
英文摘要：
BACKGROUND AND AIMS:
The ABCC2 gene is implicated in Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver disorder. The primary aim of this study was to determine the diagnostic value of ABCC2 genetic testing in the largest cohort of DJS reported to date. The high number of patients with cholestatic manifestations in this series prompted us to evaluate the genetic contribution of rare, potentially pathogenic ABCC2 variants to other inherited cholestatic disorders.
METHODS:
The cohort study included 32 patients with clinical DJS diagnosis, and 372 patients referred for the following disorders: low phospholipid-associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy (ICP) and benign recurrent intrahepatic cholestasis (BRIC). ABCC2 was screened by next-generation sequencing.
RESULTS:
Most patients with clinical DJS had positive genetic diagnosis (n = 30; 94%), with a great diversity of point mutations and copy number variations in ABCC2. Strikingly, eight (27%) of these patients showed transient cholestatic features at presentation: four neonatal cholestasis, two ICP, one contraceptive-induced cholestasis and one sporadic cholestasis. Conversely, the frequency of rare, heterozygous, potentially pathogenic ABCC2 variants in patients with LPAC, ICP or BRIC did not differ significantly from that of the general population.
CONCLUSIONS:
This large series reveals that DJS is a highly homogeneous Mendelian disorder involving a large spectrum of ABCC2 variants. Genetic testing is crucial to establish early DJS diagnosis in patients with atypical presentations, such as neonatal cholestasis. This study also provides no evidence for the contribution of rare, potentially pathogenic ABCC2 variants to other inherited cholestatic disorders.
中文摘要：
背景和目的：
ABCC2基因與Dubin-Johnson症候群（DJS）發生有關，這是一種罕見的常染色體隱性遺傳性肝病。這項研究的主要目的是，確定ABCC2基因檢測在目前為止的、最大DJS隊列中的診斷價值。該隊列中有大量膽汁淤積表現的患者，這促使我們評估這種罕見的、潛在致病性的ABCC2變異在其他遺傳性膽汁淤積性疾病發病中的作用。
方法：
該隊列研究包括32例臨床診斷的DJS患者，以及372例因以下疾病而轉診的患者：低磷脂相關性膽石症症候群（LPAC），妊娠肝內膽汁淤積症（ICP）和良性復發性肝內膽汁淤積症（BRIC）。通過二代測序檢測ABCC2變異。
結果：
大多數臨床診斷DJS的患者遺傳學診斷也為陽性（n = 30；94％），但ABCC2基因的點突變和拷貝數變異具有很大的多樣性。令人驚訝的是，這些患者中有8名（27％）表現為短暫的膽汁淤積特徵：4例新生兒膽汁淤積，2例ICP，1例避孕藥致膽汁淤積和1例偶發性膽汁淤積。相反，在LPAC，ICP或BRIC的患者中，罕見的、雜合的、潛在致病的ABCC2變異的頻率與一般人群的頻率沒有顯著差異。
結論：
這個大型隊列揭示了DJS是一種高度同質的孟德爾疾病，涉及ABCC2基因的多種變異。基因檢測對於具有非典型表現（例如新生兒膽汁淤積）的DJS的早期診斷至關重要。這項研究也表明罕見的、潛在致病性ABCC2變異對其他遺傳性膽汁淤積性疾病沒有貢獻。